Studies of the rabbit class I antigens expressed by the rabbit T cell line RL-5 have identified four distinct cDNA transcripts. Complete structural data are available for these and for a genomic clone, 19-1, corresponding to the one expressed gene (pR9) of the rabbit T cell line. Transfection of human HELA cells with 19-1 gave cells expressing the rabbit product. A second genomic sequence is available for the clone, designated pR11, and this indicates a flaw in the transmembrane region that may preclude its expression. Probes derived from the four cDNA clones and synthetic oligonucleotide probes based on their sequences were used to detect genes corresponding to them in genomic libraries and on Southern blots. These probes will be used to classify the rabbit class I genes in terms of expression in various tissues. Studies of rabbit class II antigens have begun using probes for HLA-DP, -DQ and -DR Alpha genes. These probes have been used to search genomic and cDNA libraries from the RL-5 T cell line. To date, five distinct ALpha clones have been identified based on distinct mapping patterns and on hybridization studies using the human probe and the newly derived rabbit class II probes. Rabbit genes corresponding to HLA-DR, -DP1, -DP2 and -DQ Alpha have been identified along with a fifth Alpha gene designated RLA-DN that does not correspond to any previously reported class II gene. Structural studies of the RLA Alpha genes are underway and preliminary data suggest that they have a high degree of homology to the human and Alpha genes. Expression studies of the class II genes will continue in parallel with those of the class I genes as the probes become available.